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Melior Discovery seizure potential

EEG Pro- and Anti-Convulsant Evaluation
Pro- or anti- convulsant activity can be evaluated using EEG power analysis and can be more sensitive than models utilizing chemical or electrical stimulation and behavioral outcome measures.  For example, quantitative anti-convulsant activity can be evaluated using sub-convulsant doses of PTZ that produce characteristic EEG frequency changes that can be quantitatively analyzed for several hours.

Figure A- EEG frequency time course after PTZ; Diazepam VS. Vehicle

 

                  

Sub-convulsant dose of PTZ increases low-frequency EEG power at 5 Hz for several hours after administration.  [1] Normal waking EEG pre-dosing.  Note peak in FFT record at 7-8 Hz corresponding to the theta band.  [2] Diazepman (5mg/kg) alone has little effect on EEG (27 minutes post dosing).  [3] This animal was treated with Vehicle, then 27 minutes later given PTZ (40mg/kg).  EEG recorded 26 minutes later shows periodic bursting which produced a significant increase in FFT amplitude at 5 Hz, distinct from the theta EEG (note the 5x decrease in FFT scale).  [4] Same animal as panel [2] also received PTZ at the same animal in panel [3].  In this case, Diazepam almost completely blocked PTZ-induced bursting. 

 

Figure B- Diazepam Suppresses PTZ-induced EEG Bursting:

 

                    

Bursting induced by PTZ was quantified by frequency analysis, and the effect of Diazepam evaluated.  Graph above shows significant effect of Diazepam (5mg/kg) in suppressing PTZ-induced bursting (paradigm as in Figure A; N= 5/group).  This paradigm potentially allows repeat testing of animals to determine effects of chronic or sub-chronic administration of PTZ or anti-convulsant drug. 

 

Figure C- Suppression of PTZ Bursting in Mice by Diazepam:

    

                  

 

Bursting can be induced in mice by dose-escalation of PTZ.  The graph above shows the increase in EEG power at 4-6 Hz over a period of 280 minutes during successive administration of PTZ doses totaling 140 mg/kg.  Diazepam (5 mg/kg) was then administered and within minutes suppressed the bursting. 

 

Figure D- Suppression of PTZ Bursting in Mice by Diazepam:

 

                    

Quantitative evaluation of bursting in mice and suppression by Diazepam (5mg/kg).

 

If you are interested in learning more about EEG Pro- and Anti- Convulsant Evaluation, please contact models@meliordiscovery.com to start the conversation.